Professor Sir David Klenerman FMedSci FRS

Watching single molecules in action

We are physical scientists interested in developing and applying a range of new quantitative biophysical methods, based on laser fluorescence spectroscopy and scanning probe microscopy, to important problems in biology, which have not been addressed to date due to the lack of suitable tools and hence directly image biological processes down to the level of single molecules. While our experiments range from studies of individual biomolecules to living cells, no previous biological background is required for our research and we work closely with a range of biological and clinical collaborators. We are also part of the Cambridge Dementia Research centre.

Single molecule fluorescence

By studying molecules one at time, using fluorescence, specific complexes in a mixture can be identified and analysed without the need for any separation. With our collaborators we are exploiting single molecule fluorescence spectroscopy to study a range of biologically important molecules and processes. At present our main projects are:

Imaging the early molecular events that lead to the triggering of T-cells, a process that underpins the adaptive immune response and is remarkably sensitive and selective.

Imaging the early molecular events that lead to the triggering of Toll-like receptors, a key process in the innate immune response which plays an important role in causing inflammation in neurodegenerative diseases such as Alzheimer’s disease.

Imaging and characterising the protein aggregates formed in the test-tube during aggregation reactions of disease-associated proteins and those present in human samples such as cerebral spinal fluid and brain tissue. We want to determine the aggregates responsible for causing neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease in humans and the mechanisms by which they damage cells and spread through the brain.

Determining the structure and organisation of DNA in the nucleus of cells and how this is regulated and changes during cell differentiation.

Imaging aggregates of P53 and determining the role of these aggregates in the development and spreading of cancer.

Scanning nanopipette

In collaboration with Professor Korchev at Imperial College we have developed a method based on a scanning nanopipette that allows robust, high resolution, non- contact imaging of living cells, down to the level of individual protein complexes. It can also be used to probe function by performing nanoscale assays such as locally deliver controlled amounts of reagents or performing single ion channel recording. The figure shows the University of Cambridge crest written in fluorescent DNA. We are using this method to watch the details of biological process taking place on the surface of living cells and to directly observe protein aggregates damage neuronal cells.

Two new positions available

Two PDRA positions are available from October, 2019 . For more details and to apply see: